title: Integration of left-right Pitx2 transcription and Wnt signaling drives asymmetric gut morphogenesis via Daam2.
abstract: A critical aspect of gut morphogenesis is initiation of a leftward tilt, and failure to do so leads to gut malrotation and volvulus. The direction of tilt is specified by asymmetric cell behaviors within the dorsal mesentery (DM), which suspends the gut tube, and is downstream of Pitx2, the key transcription factor responsible for the transfer of left-right (L-R) information from early gastrulation to morphogenesis. Although Pitx2 is a master regulator of L-R organ development, its cellular targets that drive asymmetric morphogenesis are not known. Using laser microdissection and targeted gene misexpression in the chicken DM, we show that Pitx2-specific effectors mediate Wnt signaling to activate the formin Daam2, a key Wnt effector and itself a Pitx2 target, linking actin dynamics to cadherin-based junctions to ultimately generate asymmetric cell behaviors. Our work highlights how integration of two conserved cascades may be the ultimate force through which Pitx2 sculpts L-R organs.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Welsh
authors.forename: Michael
authors.initials: M
authors.lastname: Thomsen
authors.forename: David W
authors.initials: DW
authors.lastname: Gludish
authors.forename: Catalina
authors.initials: C
authors.lastname: Alfonso-Parra
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Natasza A
authors.initials: NA
authors.lastname: Kurpios
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002642:Chick Embryo; D054262:Gastrulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology*; D008643:Mesentery / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D000199:Actins; D015820:Cadherins; D018398:Homeodomain Proteins; D008840:Microfilament Proteins; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins; D000097577:Homeobox Protein PITX2; C500366:Daam2 protein, mouse